Bottom Line:
Based on the prodrug principle, aspirin eugenol ester (AEE) was synthesized, which can reduce the side effects of aspirin and eugenol.The results indicated that AEE significantly not only reduced the average length of thrombus, PT values and FIB concentration, but also reduced the red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT) and platelet (PLT).From these results, it was concluded that AEE possessed positive effect on thrombosis prevention in vivo through the reduction of FIB, PLT, inhibition of platelet aggregation and the change of TT and PT values.

ABSTRACTBased on the prodrug principle, aspirin eugenol ester (AEE) was synthesized, which can reduce the side effects of aspirin and eugenol. As a good candidate for new antithrombotic and anti-inflammatory medicine, it is essential to evaluate its preventive effect on thrombosis. Preventive effect of AEE was investigated in κ-carrageenan-induced rat tail thrombosis model. AEE suspension liquids were prepared in 0.5% sodium carboxymethyl cellulose (CMC-Na). AEE was administrated at the dosage of 18, 36 and 72 mg/kg. Aspirin (20 mg/kg), eugenol (18 mg/kg) and 0.5% CMC-Na (30 mg/kg) were used as control drug. In order to compare the effects between AEE and its precursor, integration of aspirin and eugenol group (molar ratio 1:1) was also designed in the experiment. After drugs were administrated intragastrically for seven days, each rat was injected intraperitoneally with 20 mg/kg BW κ-carrageen dissolved in physiological saline to induce thrombosis. The length of tail-thrombosis was measured at 24 and 48 hours. The blank group just was given physiological saline for seven days without κ-carrageenan administrated. The results indicated that AEE significantly not only reduced the average length of thrombus, PT values and FIB concentration, but also reduced the red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT) and platelet (PLT). The effects of AEE on platelet aggregation and anticoagulant in vitro showed that AEE could inhibit adenosine diphosphate (ADP)-induced platelet aggregation as dose-dependence but no notable effect on blood clotting. From these results, it was concluded that AEE possessed positive effect on thrombosis prevention in vivo through the reduction of FIB, PLT, inhibition of platelet aggregation and the change of TT and PT values.

pone.0133125.g002: Preventive effects of aspirin, eugenol and AEE on rat tail thrombus induced by κ-carrageenan at 24 hours.Date represents two of ten animals for each group. Swelling and redness was pointed out by arrow. Integration: integration of aspirin and eugenol (molar ratio 1:1).

Mentions:
The results showed that AEE could inhibit significantly thrombus formation in κ-carrageenan-induced thrombosis model in rats (seen in Fig 1). The representative thrombus figures of each group at 24 hours were shown in Fig 2. The average thrombus length in model group was 13.63 cm at 48 hours, whereas the average lengths of thrombus in three AEE groups were 9.63, 8.96 and 9.04 cm at 48 hours. From the results, when compared with the aspirin and eugenol groups, AEE could significantly reduce the thrombus length, which demonstrated that there was a significant difference between AEE and its precursor. Interestingly, there was no significant difference between integration of aspirin and eugenol (molar ratio 1:1) group and model group. Therefore, integration of aspirin and eugenol had no antithrombotic effect, even aspirin and eugenol as two precursors of AEE. The results in vivo suggested that AEE can prevent tail thrombosis formation induced by κ-carrageenan.

pone.0133125.g002: Preventive effects of aspirin, eugenol and AEE on rat tail thrombus induced by κ-carrageenan at 24 hours.Date represents two of ten animals for each group. Swelling and redness was pointed out by arrow. Integration: integration of aspirin and eugenol (molar ratio 1:1).

Mentions:
The results showed that AEE could inhibit significantly thrombus formation in κ-carrageenan-induced thrombosis model in rats (seen in Fig 1). The representative thrombus figures of each group at 24 hours were shown in Fig 2. The average thrombus length in model group was 13.63 cm at 48 hours, whereas the average lengths of thrombus in three AEE groups were 9.63, 8.96 and 9.04 cm at 48 hours. From the results, when compared with the aspirin and eugenol groups, AEE could significantly reduce the thrombus length, which demonstrated that there was a significant difference between AEE and its precursor. Interestingly, there was no significant difference between integration of aspirin and eugenol (molar ratio 1:1) group and model group. Therefore, integration of aspirin and eugenol had no antithrombotic effect, even aspirin and eugenol as two precursors of AEE. The results in vivo suggested that AEE can prevent tail thrombosis formation induced by κ-carrageenan.

Bottom Line:
Based on the prodrug principle, aspirin eugenol ester (AEE) was synthesized, which can reduce the side effects of aspirin and eugenol.The results indicated that AEE significantly not only reduced the average length of thrombus, PT values and FIB concentration, but also reduced the red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT) and platelet (PLT).From these results, it was concluded that AEE possessed positive effect on thrombosis prevention in vivo through the reduction of FIB, PLT, inhibition of platelet aggregation and the change of TT and PT values.

ABSTRACTBased on the prodrug principle, aspirin eugenol ester (AEE) was synthesized, which can reduce the side effects of aspirin and eugenol. As a good candidate for new antithrombotic and anti-inflammatory medicine, it is essential to evaluate its preventive effect on thrombosis. Preventive effect of AEE was investigated in κ-carrageenan-induced rat tail thrombosis model. AEE suspension liquids were prepared in 0.5% sodium carboxymethyl cellulose (CMC-Na). AEE was administrated at the dosage of 18, 36 and 72 mg/kg. Aspirin (20 mg/kg), eugenol (18 mg/kg) and 0.5% CMC-Na (30 mg/kg) were used as control drug. In order to compare the effects between AEE and its precursor, integration of aspirin and eugenol group (molar ratio 1:1) was also designed in the experiment. After drugs were administrated intragastrically for seven days, each rat was injected intraperitoneally with 20 mg/kg BW κ-carrageen dissolved in physiological saline to induce thrombosis. The length of tail-thrombosis was measured at 24 and 48 hours. The blank group just was given physiological saline for seven days without κ-carrageenan administrated. The results indicated that AEE significantly not only reduced the average length of thrombus, PT values and FIB concentration, but also reduced the red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT) and platelet (PLT). The effects of AEE on platelet aggregation and anticoagulant in vitro showed that AEE could inhibit adenosine diphosphate (ADP)-induced platelet aggregation as dose-dependence but no notable effect on blood clotting. From these results, it was concluded that AEE possessed positive effect on thrombosis prevention in vivo through the reduction of FIB, PLT, inhibition of platelet aggregation and the change of TT and PT values.